Conventional antibodies of vertebrates are composed of paired heavy (H) and light (L) polypeptide chains. Absence of heavy chain (HC) or light chain (LC) expression leads to arrest of B cell development. Some species such as camelids (camels, dromedaries and llamas), sharks, and raffish produce HC-only antibodies (HcAb) that lack L-chains as part of their normal. B cell development and repertoire. The antigen-binding site, a single-variable domain (VHH), resembles VU of conventional Abs. In Cameliclae, these heavy-chain antibodies (HcAbs) belong to IgG2 and IgG3 isotypes, and their variable domains are subject to somatic hypermutation. Thus, the camelid HcAbs are affinity-matured and functional in antigen binding.
Transgenic mice containing rearranged dromedary γ2a heavy chains have been generated. The dromedary transgene is expressed as heavy chain-only antibodies. See, Zou X. et al, Journal of Immunology, 175: 3769-3779 (2005). Mice containing various non-rearranged chimeric HcAb loci have also been generated. See, Janssens R. et al. PNAS, 103 (41): 15130-15135 (2006). The limited number of VH fragments in the transgenic HcAb loci, however, results in some antigens not being recognized by these mice, despite potent antigen response by wildtype mice. See, Janssens R. et al. PNAS, 103 (41): 15130-15135 (2006); Drabe D. et al. Frontiers in Immunology, 7 (619): 1-10 (2016); and U.S. Pat. No. 8,883,150. Heavy chain-only antibodies are also spontaneously produced in light chain deficient mice, but in these mice, B cell development is blocked at the immature B cell stage. See, Zou X. et al. JEM, 204(13): 3271-3283 (2007).
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